Pyrvinium Pamoate Enhances the Anti-cancer Activities of Gemcitabine in Pancreatic Cancer DOI Open Access
Karabo Serala, Jinming Bai, Sharon Prince

et al.

Published: Feb. 29, 2024

Pancreatic cancer is an intractable disease with the worst prognosis of all cancers. The currently used treatment regimens do not significantly impact patient survival, and therefore, effective strategies are urgently needed. Drug repurposing, which identifies new indications for existing approved drugs, has proven to be a promising approach anti-cancer drug discovery. Indeed antihelmintic drug, pyrvinium pamoate shown promise as anti-pancreatic but date, inhibition mitochondrial function only mechanism action described in pancreatic cancer. This study showed, using 2D cell cultures 3D spheroids, that exhibited short- long-term cytotoxicity, inhibited epithelial-to-mesenchymal transition invasion migration. Mechanistically, induced DNA damage, PI3K/AKT survival pathway, triggered cycle arrests, well apoptotic autophagic death. Importantly, acted synergistically first-line gemcitabine culture models. provided evidence single agent combination

Language: Английский

Drug repurposing for cancer therapy DOI Creative Commons
Ying Xia, Ming Sun, Hai Huang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

Citations

110
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

16
Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response DOI Creative Commons
Stefanie Höfer, Larissa Frasch,

Sarah Brajkovic

et al.

Molecular Systems Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

Citations

1
The evidence for repurposing anti-epileptic drugs to target cancer DOI Creative Commons

Mir Aroosa,

Jonaid Ahmad Malik,

Sakeel Ahmed

et al.

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(9), P. 7667 - 7680

Published: July 7, 2023

Antiepileptic drugs are versatile with the potential to be used in functional drug formulations repurposing approaches. In present review, we investigated anticancer properties of antiepileptic and interlinked cancer epileptic pathways. Our focus was primarily on those that have entered clinical trials positive results provided good preclinical studies. Many contributing factors make therapy fail, like resistance, tumor heterogeneity, cost; exploring all alternatives for efficient treatment is important. It crucial find new targets out antitumor molecules from already clinically validated approved utilizing methods. The advancements genomics, proteomics, other computational approaches speed up repurposing. This review summarizes different cancers progression brain. Valproic acid, oxcarbazepine, lacosamide, lamotrigine, levetiracetam showed beneficial outcomes against cancers. might a option adjuvant therapy, but there need investigate further their efficacy trials.

Language: Английский

Citations

15
Resveratrol Derivative Exhibits Marked Antiproliferative Actions, Affecting Stemness in Pancreatic Cancer Cells DOI Open Access
Rosalba Florio, Barbara De Filippis, Serena Veschi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1977 - 1977

Published: Jan. 19, 2023

Pancreatic cancer (PC) is one of the deadliest malignancies, with an increasing incidence and limited response to current therapeutic options. Therefore, more effective low-toxic agents are needed improve PC patients' outcomes. Resveratrol (RSV) a natural polyphenol multiple biological properties, including anticancer effects. In this study, we explored antiproliferative activities newly synthetized RSV analogues in panel cell lines evaluated physicochemical properties most active compound. This derivative exhibited marked effects cells through mechanisms involving DNA damage, apoptosis induction, interference cycle progression, as assessed using flow cytometry immunoblot analysis proteins, PARP cleavage, H2AX phosphorylation. Notably, compound induced consistent reduction subpopulation CD133+EpCAM+ stem-like phenotype, paralleled by dramatic on clonogenicity. Moreover, had negligible toxicity against normal HFF-1 and, thus, good selectivity index values toward lines. Remarkably, its higher lipophilicity stability human plasma, compared RSV, might ensure better permeation along gastrointestinal tract. Our results provide insights into action contributing activity synthetic analogue, supporting potential value search for safe treatment.

Language: Английский

Citations

14
Molecular Mechanisms of Chloroquine and Hydroxychloroquine Used in Cancer Therapy DOI
Juan Bautista De Sanctis, Jaime Charris, Zuleyma Blanco

et al.

Anti-Cancer Agents in Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 23(10), P. 1122 - 1144

Published: May 22, 2022

Abstract: Tumour relapse, chemotherapy resistance, and metastasis continue to be unsolved issues in cancer therapy. A recent approach has been scrutinise drugs used the clinic for other illnesses modify their structure increase selectivity cells. Chloroquine (CQ) hydroxychloroquine (HCQ), known antimalarials, have successfully treated autoimmune neoplastic diseases. CQ HCQ, well-known lysosomotropic agents, induce apoptosis, downregulate autophagy, tumour microenvironment. Moreover, they affect Toll 9/NF-κB receptor pathway, activate stress response pathways, enhance p53 activity CXCR4-CXCL12 expression cells, which would help explain effects treatment. These compounds can normalise tumourassociated vasculature, promote activation of immune system, change phenotype tumour-associated macrophages (from M2 M1), stimulate cancer-associated fibroblasts. We aim review historical aspects its derivatives most relevant mechanisms that support therapeutic use HCQ treatment cancer.

Language: Английский

Citations

19
Metformin use and pancreatic ductal adenocarcinoma outcomes: a narrative review DOI Open Access

D.H. Lee,

Mun Sem Liew,

Spiros Fourlanos

et al.

ANZ Journal of Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Background Metformin is a diabetes medication with anti‐mitotic properties. A narrative review was performed to investigate people using metformin and the risk of developing pancreatic ductal adenocarcinoma (PDAC) as well survival outcomes in established PDAC. Methods Relevant studies on use PDAC were retrieved from PubMed including observational PDAC, randomized controlled trials treatment Results Of 367 searched, 26 fulfilled criteria for this review. not consistently associated reduced However, use, especially higher cumulative doses, some longer patients subgroup resectable more advanced (non‐resectable metastatic) Conclusion may be overall benefits but metastatic subgroup. The evidence date does support routine an adjuvant therapy

Language: Английский

Citations

0
Drug Repurposing in Pancreatic Cancer: A Multi-Stakeholder Perspective to Improve Treatment Options for Pancreatic Cancer Patients DOI Creative Commons
Eric W. Hewitt, Gauthier Bouche,

Alexandre Alencar

et al.

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 429 - 440

Published: March 1, 2025

Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective less toxic drugs improve dismal prognosis PC. In recent years, drug repurposing (DR) has emerged as attractive strategy identify novel treatments PC by leveraging existing approved other indications. Through use electronic medical records, Artificial Intelligence, study metabolic pathways, signalling many approaches, it become much easier in years potential uses old drugs. Although policy, funding research attention this area steadily growing, major challenges efficient patient-centric DR be addressed. These include but not limited regulatory, financial barriers lack coordination collaboration among several sectors stakeholders. To explore opportunities associated with PC, a one-day multi-stakeholder meeting was held on 14th November 2024 Brussels, Belgium part REMEDi4ALL project. This provided platform researchers, clinicians, industry representatives, funders, regulatory experts, patient advocates discuss propose actions optimize accelerate Insights from support enhance treatment while highlighting importance systemic supportive changes policy landscapes, interdisciplinary collaboration, data sharing, involvement driving innovation. summary highlights key outcomes recommendations informing future efforts advance initiatives context

Language: Английский

Citations

0
Niclosamide-Loaded Polyanhydride Nanoparticles to Combat Gemcitabine Resistance in Pancreatic Cancer DOI Creative Commons
Brianna M. White, Venugopal Gunda, Susheel Kumar Nethi

et al.

Regenerative Engineering and Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy DOI Open Access

Noor Tarawneh,

S. A. Hussein,

Shtaywy Abdalla

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2673 - 2673

Published: April 14, 2025

Epilepsy is a neurological disorder characterized by repeated convulsions. Antiepileptic drugs (AEDs) are the main course of therapy for epilepsy. These medications given according to each patient’s personal medical history and types seizures they suffer. They have been employed decades manage epilepsy, thus delivering relief from through numerous mechanisms action. Aside their anticonvulsant attributes, current evidence suggests that certain AEDs may display potential inhibitory effects against cancer invasion metastasis. This review explored complicated interactions between modes action pathways causing cancer, impact on metastasis various forms while addressing associated side effects. For example, valproic acid inhibits histone deacetylase, hyperacetylation genes, especially those regulating cell cycle, culminating in cycle arrest. Topiramate carbonic anhydrase, disrupting acidic microenvironment needed cells thrive. Lacosamide increases slow inactivation voltage gated Na+ channel, inhibiting growth, proliferation, many cancers. Although drug development complex task due regulatory, intellectual property, economic challenges, researchers exploring repurposing tactics overcome these challenges find new therapeutic alternatives diseases like cancer. Thus, considered among most effective ways develop candidates using novel properties characteristics, this also discusses issues.

Language: Английский

Citations

0